Abstract Patients with rheumatoid arthritis (RA) often require alterations of their therapeutic regimen throughout the course of their illness, guided by specific outcomes in line with the treat-to-target principle. Importantly, a significant portion of the RA population fails to achieve sufficient disease control in the long term. Several years ago, the umbrella notion of difficult-to-treat (D2T) RA was introduced to facilitate more structured care and research efforts for patients who remain symptomatic despite having received multiple courses of targeted medications. D2T RA represents a heterogeneous condition sustained by a complex interplay of underlying factors. Biological therapies and Janus kinase inhibitors have demonstrated efficacy in alleviating disease activity in patients refractory to conventional treatments. The use of tailored non-pharmacological therapies (physiotherapy, psychological interventions, etc.) to complement pharmacotherapy chiefly addresses symptoms unrelated to ongoing inflammation. In this narrative review, we examine the current use and relevance of pharmacological and non-pharmacological approaches for D2T RA.
Nagy et al. (2026) studied this question.